Edward Kravitz

Last updated
Edward Kravitz
Born (1932-12-19) December 19, 1932 (age 91)
New York City, U.S.
Alma mater City College of New York (BS)
University of Michigan (PhD)
Known forIdentifying gamma-aminobutyric acid (GABA) as a neurotransmitter
Awards
Scientific career
Fields Neuroscience
Institutions National Institute of Health
Harvard Medical School
Doctoral students Margaret Livingstone
Thomas Schwarz

Edward Arthur Kravitz (born December 19, 1932) is an American neuroscientist who is the George Packer Berry Professor of Neurobiology at Harvard Medical School. [1] He is widely recognized for demonstrating that gamma-aminobutyric acid (GABA) functions as a neurotransmitter. [2] In addition, he and Antony Stretton were the first to use the intracellular dye procion yellow to visualize neuronal architecture. [3]

Contents

Kravitz's work with neuroamines demonstrated that serotonin and octopamine act as synaptic modulators. Kravitz continued to explore the function of amines using Homarus americanus , the American lobster, as a model organism to study aggression. He currently works on aggressive behavior using the genetically manipulable model organism, Drosophila melanogaster , the fruit fly.

Personal life

Ed Kravitz was born in New York to Ada Machlus and Isadore Kravitz. He had one older brother, Bill (1929-2014). Kravitz grew up in The Bronx during the Great Depression. More than once he skipped an entire grade in order to be challenged in school and ended up in college at age 16. [4] Ed met his wife Kathryn Anne Frakes at the University of Michigan; they were married in 1959. Together they have two sons, David [5] (b. February 21, 1964) and James [6] (b. May 14, 1966), and one granddaughter, Theodora (b. August 9, 2022).

Scientific career

After graduating from Evander Childs High School in The Bronx, Kravitz remained in the neighborhood he grew up in and began his studies at City College of New York (CCNY). In 1954 he graduated from CCNY with a double major in Biology and Chemistry. Unsure of what to do next, Kravitz applied to be an officer in the U.S. Army Medical Corps as well as to two medical schools, and for a Research Assistant position.[ citation needed ] He ended up at Sloan-Kettering in the laboratory of George Tarnowski. Under the supervision of George Tarnowski, Lou Kaplan, a young biochemist at the time, and Christine Riley, director of the chemotherapy unit, Kravitz began an independent research project studying amino acid metabolism in ascites tumor cells. It was this experience that led to Kravitz's decision to pursue a career as a Scientist.[ citation needed ] In 1954, Kravitz began graduate school at the University of Michigan. He met a lot of great colleagues at this time, including Marshall Nirenberg with whom he shared an apartment on Huron Avenue in Ann Arbor.[ citation needed ] Kravitz's thesis work was done in the laboratory of Armand Guarino and led to his first paper “On the effect of inorganic phosphate on hexose phosphate metabolism” which was published in the journal Science. In 1959 he received his Ph.D. in Biological Chemistry and began working in Earl Stadtman's laboratory at the National Institutes of Health. Although at one time Kravitz planned on pursuing two additional post-doctoral positions after studying morphine metabolism in the Stadtman laboratory, he was recruited to Harvard Medical School by Steve Kuffler in 1960. Almost immediately, he began working with Steve Kuffler, Dave Potter and Nico van Gelder on the experiments that would eventually demonstrate that GABA functions as a neurotransmitter. From his biochemistry training and friends at NIH, Kravitz knew that by growing Pseudomonas fluorescens on GABA as a sole carbon source, an enzymatic assay could be used to quantify the amount of GABA in the neurons of crustaceans. Using this enzymatic assay, the group quickly learned that GABA was highly expressed in inhibitory neurons. Later Kravitz worked with Masanori Otsuka, Les Iversen, and Zach Hall to show that GABA was released from inhibitory neurons of lobsters. [7] While today Ed's work on GABA is well respected, it was quite controversial when first presented publicly.[ citation needed ] After his first talk on the work at the Marine Biological Laboratory in Woods Hole, David Nachmanson commented “Well, we don’t know what that little bit of an amino acid that you see being released is when you stimulate a nerve, but it certainly is not a chemical transmitter compound, because we all know that transmission is electrical”. [8]

The second project Kravtiz took on in the mid-1960s was much more anatomical in nature. In collaboration with his postdoctoral fellow, Antony Stretton, Ed began developing a technique to visualize the structure of neurons in order to determine whether neuronal shapes are genetically specified. Two other Scientists at Harvard Medical School, Ed Furshpan and Jaime Alvarez, had been using intracellular dyes to localize their recording electrodes in the brains of fish, but none of their dyes were able to stain the neuropil processes of the injected neurons. Kravitz and Stretton contacted Imperial Chemicals, a manufacturer of fabric staining dyes located in Providence, RI and obtained over 120 dyes to inject into lobster neurons. In the end they found a single dye, Procion Yellow, that was highly soluble, readily released from microelectrodes, completely filled cells and their processes, survived fixation and dehydration, and, most importantly, was fluorescent. Using Procion Yellow, Kravitz, Stretton, and Edith Maier found that neurons from two different animals had strikingly similar morphological shapes. They eventually injected over 100 physiologically identified neurons, processed and sectioned the ganglia, and reconstructed the cell shapes by hand from photographs of the serial sections. [9]

In the 1970s Kravitz's laboratory turned their focus back to neurotransmitters. After finding evidence that glutamate acts as an excitatory transmitter in crustaceans, they found that acetylcholine functions as the lobster sensory transmitter compound. Around this time, the laboratory also began experimenting with the neuroamines serotonin and octopamine. By trying to understand how naturally occurring neuromodulators might act, Margaret Livingstone, a graduate student at the time, injected serotonin or octopamine into two different lobsters. The results were surprising: the lobster injected with serotonin stood tall and looked just like a dominant animal while the lobster injected with octopamine adopted a lowered posture and looked like a subordinate animal. [10] These lobster injection experiments were the birth of the aggressive behavior studies that are still ongoing in Kravitz's laboratory today.

In the 1980s and 1990s Kravitz's laboratory evolved into a neuroethology laboratory. In collaboration with his postdoctoral fellow Robert Huber, a quantitative analysis of lobster fighting behavior was underway. Lobsters proved to be an excellent model system for studies on aggression due to the ease in getting animals to fight and the fact that anatomical and physiological studies were possible. However, Kravitz soon realized that in order to discover new neurons and pathways that were important for aggression, he needed an organism whose genome was sequenced and where genetic methods were available for solving sophisticated problems, leading to work with Drosophila melanogaster.[ citation needed ]

Honors and awards (partial list)

Related Research Articles

<span class="mw-page-title-main">Neurotransmitter</span> Chemical substance that enables neurotransmission

A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell.

<span class="mw-page-title-main">GABA</span> Main inhibitory neurotransmitter in the mammalian brain

GABA is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

<span class="mw-page-title-main">Tetanus toxin</span> Extremely potent neurotoxin

Tetanus toxin (TeNT) is an extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is also called spasmogenic toxin, tentoxilysin, tetanospasmin, or tetanus neurotoxin. The LD50 of this toxin has been measured to be approximately 2.5–3 ng/kg, making it second only to the related botulinum toxin (LD50 2 ng/kg) as the deadliest toxin in the world. However, these tests are conducted solely on mice, which may react to the toxin differently from humans and other animals.

An inhibitory postsynaptic potential (IPSP) is a kind of synaptic potential that makes a postsynaptic neuron less likely to generate an action potential. The opposite of an inhibitory postsynaptic potential is an excitatory postsynaptic potential (EPSP), which is a synaptic potential that makes a postsynaptic neuron more likely to generate an action potential. IPSPs can take place at all chemical synapses, which use the secretion of neurotransmitters to create cell-to-cell signalling. EPSPs and IPSPs compete with each other at numerous synapses of a neuron. This determines whether an action potential occurring at the presynaptic terminal produces an action potential at the postsynaptic membrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.

Neurochemistry is the study of chemicals, including neurotransmitters and other molecules such as psychopharmaceuticals and neuropeptides, that control and influence the physiology of the nervous system. This particular field within neuroscience examines how neurochemicals influence the operation of neurons, synapses, and neural networks. Neurochemists analyze the biochemistry and molecular biology of organic compounds in the nervous system, and their roles in such neural processes including cortical plasticity, neurogenesis, and neural differentiation.

A neurochemical is a small organic molecule or peptide that participates in neural activity. The science of neurochemistry studies the functions of neurochemicals.

<span class="mw-page-title-main">GABA receptor</span> Receptors that respond to gamma-aminobutyric acid

The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory compound in the mature vertebrate central nervous system. There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels ; whereas GABAB receptors are G protein-coupled receptors, also called metabotropic receptors.

<span class="mw-page-title-main">Ligand-gated ion channel</span> Type of ion channel transmembrane protein

Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in response to the binding of a chemical messenger (i.e. a ligand), such as a neurotransmitter.

Molecular neuroscience is a branch of neuroscience that observes concepts in molecular biology applied to the nervous systems of animals. The scope of this subject covers topics such as molecular neuroanatomy, mechanisms of molecular signaling in the nervous system, the effects of genetics and epigenetics on neuronal development, and the molecular basis for neuroplasticity and neurodegenerative diseases. As with molecular biology, molecular neuroscience is a relatively new field that is considerably dynamic.

<span class="mw-page-title-main">Neuromodulation</span> Regulation of neurons by neurotransmitters

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

<span class="mw-page-title-main">Median raphe nucleus</span> Brain region having polygonal, fusiform, piriform neurons

The median raphe nucleus, also known as the nucleus raphes medianus (NRM) or superior central nucleus, is a brain region composed of polygonal, fusiform, and piriform neurons, which exists rostral to the nucleus raphes pontis. The MRN is located between the posterior end of the superior cerebellar peduncles and the V. Afferents of the motor nucleus. It is one of two nuclei, the other being the dorsal raphe nucleus (DnR), in the midbrain-pons.

<span class="mw-page-title-main">Synaptic potential</span> Potential difference across the postsynaptic membrane

Synaptic potential refers to the potential difference across the postsynaptic membrane that results from the action of neurotransmitters at a neuronal synapse. In other words, it is the “incoming” signal that a neuron receives. There are two forms of synaptic potential: excitatory and inhibitory. The type of potential produced depends on both the postsynaptic receptor, more specifically the changes in conductance of ion channels in the post synaptic membrane, and the nature of the released neurotransmitter. Excitatory post-synaptic potentials (EPSPs) depolarize the membrane and move the potential closer to the threshold for an action potential to be generated. Inhibitory postsynaptic potentials (IPSPs) hyperpolarize the membrane and move the potential farther away from the threshold, decreasing the likelihood of an action potential occurring. The Excitatory Post Synaptic potential is most likely going to be carried out by the neurotransmitters glutamate and acetylcholine, while the Inhibitory post synaptic potential will most likely be carried out by the neurotransmitters gamma-aminobutyric acid (GABA) and glycine. In order to depolarize a neuron enough to cause an action potential, there must be enough EPSPs to both depolarize the postsynaptic membrane from its resting membrane potential to its threshold and counterbalance the concurrent IPSPs that hyperpolarize the membrane. As an example, consider a neuron with a resting membrane potential of -70 mV (millivolts) and a threshold of -50 mV. It will need to be raised 20 mV in order to pass the threshold and fire an action potential. The neuron will account for all the many incoming excitatory and inhibitory signals via summative neural integration, and if the result is an increase of 20 mV or more, an action potential will occur.

Neurotransmitter transporters are a class of membrane transport proteins that span the cellular membranes of neurons. Their primary function is to carry neurotransmitters across these membranes and to direct their further transport to specific intracellular locations. There are more than twenty types of neurotransmitter transporters.

<span class="mw-page-title-main">GABA receptor agonist</span> Category of drug

A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors also produce sedative effects. Furthermore, they lead to changes in gene transcription.

<span class="mw-page-title-main">GABA transporter type 1</span> Protein-coding gene in the species Homo sapiens

GABA transporter 1 (GAT1) also known as sodium- and chloride-dependent GABA transporter 1 is a protein that in humans is encoded by the SLC6A1 gene and belongs to the solute carrier 6 (SLC6) family of transporters. It mediates gamma-aminobutyric acid's translocation from the extracellular to intracellular spaces within brain tissue and the central nervous system as a whole.

GABA transporters are a family of neurotransmitter / sodium symporters, belonging to the solute carrier 6 (SLC6) family. They are found in various regions of the brain in different cell types, such as neurons and astrocytes.

<span class="mw-page-title-main">GABA reuptake inhibitor</span> Drug class

A GABA reuptake inhibitor (GRI) is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid (GABA) by blocking the action of the gamma-Aminobutyric acid transporters (GATs). This in turn leads to increased extracellular concentrations of GABA and therefore an increase in GABAergic neurotransmission. Gamma-aminobutyric acid (GABA) is an amino acid that functions as the predominant inhibitory neurotransmitter within the central nervous system, playing a crucial role in modulating neuronal activity in both the brain and spinal cord. While GABA predominantly exerts inhibitory actions in the adult brain, it has an excitatory role during developmental stages. When the neuron receives the action potential, GABA is released from the pre-synaptic cell to the synaptic cleft. After the action potential transmission, GABA is detected on the dendritic side, where specific receptors collectively contribute to the inhibitory outcome by facilitating GABA transmitter uptake. Facilitated by specific enzymes, GABA binds to post-synaptic receptors, with GABAergic neurons playing a key role in system regulation. The inhibitory effects of GABA diminish when presynaptic neurons reabsorb it from the synaptic cleft for recycling by GABA transporters (GATs). The reuptake mechanism is crucial for maintaining neurotransmitter levels and synaptic functioning. Gamma-aminobutyric acid Reuptake Inhibitors (GRIs) hinder the functioning of GATs, preventing GABA reabsorption in the pre-synaptic cell. This results in increased GABA levels in the extracellular environment, leading to elevated GABA-mediated synaptic activity in the brain.

<span class="mw-page-title-main">Wade Regehr</span> Professor of Neurobiology

Wade G. Regehr is a Professor of Neurobiology at Harvard Medical School's Department of Neurobiology.

Antony "Tony" Oliver Ward Stretton is a neuroscientist, faculty member of the Neuroscience Training Program, and the John Bascom Professor of Zoology at the University of Wisconsin–Madison. He is married to fellow scientist, Philippa Claude, daughter of Albert Claude.

<span class="mw-page-title-main">Department of Neurobiology, Harvard Medical School</span> Academic Department at Harvard University Medical School, USA

The Department of Neurobiology at Harvard Medical School is located in the Longwood Medical Area of Boston, MA. The Department is part of the Basic Research Program at Harvard Medical School, with research pertaining to development of the nervous system, sensory neuroscience, neurophysiology, and behavior. The Department was founded by Stephen W. Kuffler in 1966, the first department dedicated to Neurobiology in the world. The mission of the Department is “to understand the workings of the brain through basic research and to use that knowledge to work toward preventive and therapeutic methods that alleviate neurological diseases”.

References

  1. ↑ "Edward Kravitz - Department of Neurobiology". neuro.hms.harvard.edu. February 2022.
  2. ↑ Gelder, N. M. Van; Potter, D. D.; Kravitz, E. A. (1 April 1962). "Gamma-Aminobutyric Acid and Other Blocking Substances extracted from Crab Muscle". Nature. 194 (4826): 382–383. doi:10.1038/194382b0. PMID   14459471.
  3. ↑ Kravitz, E. A.; Stretton, A. O. W. (4 October 1968). "Neuronal Geometry: Determination with a Technique of Intracellular Dye Injection". Science. 162 (3849): 132–134. doi:10.1126/science.162.3849.132. PMID   4175300.
  4. ↑ Camhi, J. (1 March 2000). "Introduction to the King Solomon Lecture of Edward Kravitz". Journal of Comparative Physiology A. 186 (3): 219–220. doi:10.1007/s003590050422. PMID   10757237.
  5. ↑ "David Kravitz, Baritone". www.davidkravitz.com.
  6. ↑ "Jamie Kravitz, UX Designer - Portfolio - Wireframes, Prototypes, Usability Testing, Evaluation, Research". www.digivitz.com.
  7. ↑ "Otsuka M., Iversen L.L., Hall Z.W., Kravitz E.A. 1966. Release of gamma-aminobutyric acid from inhibitory nerves of lobster. Proc Natl Acad Sci U S A. 56: p.1110-5". nih.gov.
  8. ↑ "Kravitz, E.A. 2003. My life up to now. In Squire L. (ed) The History of Neuroscience in Autobiography, Volume 4. Academic Press, NY p.280-343". elsevier.com.
  9. ↑ International Society for Neuroethology Newsletter March 2000 Archived 2007-08-16 at the Wayback Machine
  10. ↑ Kravitz, Edward A.; Harris-Warrick, Ronald M.; Livingstone, Margaret S. (4 April 1980). "Serotonin and Octopamine Produce Opposite Postures in Lobsters". Science. 208 (4439): 76–79. doi:10.1126/science.208.4439.76. PMID   17731572.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.